BACKGROUND: A complex inflammatory response associated with the use of cardiopulmonary bypass may ultimately lead to organ dysfunction. We investigate the effect of continuing ventilation during cardiopulmonary bypass on inflammatory reactions and cardiopulmonary function. METHODS: Fifty patients undergoing cardiopulmonary bypass were prospectively randomized to continuous ventilation and nonventilation groups. Plasma interleukin-8, interleukin-10, matrix metalloproteinase-9, tissue inhibitor metalloproteinase-1, and thromboxane B2 levels were measured preoperatively, at 1, 4, and 6 hours after aortic declamping. Levels of these mediators were also determined in bronchoalveolar lavage preoperatively and four hours after declamping. Seven parameters of cardiopulmonary function, including dynamic compliance and systemic vascular resistance, were recorded during the same time points. RESULTS: Plasma interleukin-10 levels were higher at 6 hours and tissue inhibitor metalloproteinase-1 levels were higher at 1 hour after aortic declamping in the continuous ventilation compared with the nonventilation group (p = 0.04 and 0.002, respectively), while bronchoalveolar lavage levels of tissue inhibitor metalloproteinase-1 were also higher in the continuous ventilation group 4 hours after declamping (p = 0.02). Plasma interleukin-8 levels were higher at 4 hours after declamping in the nonventilation group (p = 0.04). Postoperative dynamic compliance was better preserved in continuous ventilation patients than nonventilation patients at 6 hours after declamping (p = 0.0008). CONCLUSIONS: Continued ventilation during cardiopulmonary bypass results in lesser inflammatory and proteolytic responses, and may better preserve pulmonary function than cardiopulmonary bypass without ventilation.